The sterilizing and mutagenic action of chemotherapeutic drugs and radiation on male germ cells will be investigated. The goal is to better understand the action of antineoplastic agents on male germ cells so that the potential risks to treated cancer patients can be predicted and minimized. Mice will be used to test basic mechanisms and to screen treatment regimens. Data will also be obtained from treated patients and compared to results on the mouse. Where differences exist, rats and monkeys will also be used as test systems. Quantitative measurements of mouse testicular stem cell survival will be performed after various treatment schedules, with single or combinations of agents. Possible factors responsible for variations in stem cell sensitivity, such as cell cycle phase, proliferative state, oxygen levels, or hormonal conditions, will be examined. The effects of chemotherapy and radiotherapy on human sperm production will be studied, both prospectively and retrospecitively. Patients with hodgkin's disease, non-Hodgkin's lymphormas, and chronic myelogenous leukemia, and those treated with fast neutron radiotherapy will be selected for detailed study. Semen samples will be obtained prior to, during, and at intervals after therapy. Sperm counts, motility, and morphology will be examined and correlated with the treatment modality and dosage, time after treatment, and individual patient characteristics. Sperm analysis of untreated cancer patients will be analyzed to determine the effects of the disease on sperm production. Methods of protection against the sterilizing effects of cancer therapy will be investigated. Enzymatic protectors, radioprotectors, hormonal methods, and vasoconstriction by drugs or hypothermia will be tested. Tests will first be performed in rodents. If results are positive, protocols for clinical investigation will be designed. The mutagenic potential of antineoplastic agents will be investigated in mice and men. Chromosomal damage in spermatocytes derived from treated stem cells will be assessed. Flow cytometry will be used to detect meiotic nodisjunction and diploidy in spermatids and spermatozoa. Sperm head abnormalities will be scored s a possible indicator of mutagenic damage. Counts of fluorescent Y-bodies will also be performed on human sperm. Abnormalities induced by therapy will be correlated with treatment received.**